摘要
目的:报道1例Ras基因相关性自身免疫淋巴增殖性疾病(Ras-associated autoimmune leukoproliferative disorder,RALD)的病史并探讨RALD的临床特征、基因特点、治疗方法,以提高对本病的认识。方法 :回顾性分析2012年9月至2019年1月于我科诊治的1例RALD患儿临床资料并复习相关文献。结果 :患儿男性,8岁,反复肝肿大、脾肿大6年余,全身淋巴结肿大1年余。2012年8月及2014年8月曾2次因发热、肝大、脾大、外周血三系下降诊断为噬血细胞淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH),按照HLH方案化疗后完全缓解。2018年4月症状再次出现反复,骨髓涂片、肝穿刺及淋巴结活检排除肿瘤性疾病,基因测序发现NRAS基因c.38G>A(p.G13D)杂合突变,考虑诊断RALD,给予肾上腺糖皮质激素等治疗缓解,于2018年10月行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation, allo-HSCT),随访稳定至今。文献共检索到RALD病例25例,其中NRAS突变12例,KRAS突变13例,多为学龄前起病,以肝肿大、脾肿大、淋巴组织增生、自身免疫性血细胞减少、B细胞或单核细胞增多、高γ球蛋白血症等为主要表现,病情多良性迁延,但有白血病、淋巴瘤发病报道,与幼年型粒单核细胞白血病(juvenile myelomonocytic leukemia,JMML)难鉴别。免疫抑制治疗一般有效,其中仅1例患者接受allo-HSCT治疗后痊愈。结论:RALD初始症状不典型,症状发展、治疗相关反应以及多组织基因验证有助于诊断,allo-HSCT对于体细胞突变所致RALD患者治疗有效。
Objective To summarize and review the clinical data of a case with Ras-associated autoimmune leukoproliferative disorder(RALD) caused by somatic mutation in NRAS gene and explore the clinical features, gene characteristics and treatment of RALD. Methods The clinical and laboratory data of a case RALD treated with allo-hematopoietic stem cell transplantation(allo-HSCT) in our hospital were retrieved and retrospectively analyzed. The related literature was reviewed. Results The eight-year old boy was admitted for recurrent hepatosplenomegaly and systemic lymphadenopathy.With enlarged liver and spleen, decrease of peripheral blood and fever, the patient was diagnosed as hemophagocytic lymphohistiocytosis(HLH) initially and achieved complete remission with HLH treatment regimen. However, the symptom relapsed and further pathological study including bone marrow smears, liver puncture and lymph node biopsy excluded malignancies. Whole exon sequencing revealed heterozygous c.38 G >A(p.G13 D) mutation in NRAS gene and diagnosis of RALD was established. Allo-HSCT was performed when complete remission was induced, and the patient remained disease free since then. A total of 25 cases caused by NRAS(12 cases) or KRAS(13 cases) gene mutation were retrieved from literature search and most of the cases presented primarily with hypergammaglobulinemia, splenomegaly, B cells hyperplasia or mononucleosis. Mostly benign with long duration, the condition occasionally presented as leukemia and lymphoma, which were difficult to distinguish from juvenile myelomonocytic leukemia(JMML). Immunosuppressive therapy is generally effective. The allo-HSCT was attempted and successful in a case. Conclusions The RALD usually has nontypical clinical presentations and comprehensive analysis of symptoms, treatment response and genetic study of multiple tissue samples are helpful for prompt diagnosis. The allo-HSCT is effective in the treatment of RALD patients caused by somatic mutations.
作者
张婧
朱华
罗成娟
薛惠良
罗长缨
ZHANG Jing;ZHU Hua;LUO Chengjuan;XUE Huiliang;LUO Changying(Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine Shanghai 200127,China)
出处
《内科理论与实践》
2020年第5期347-351,共5页
Journal of Internal Medicine Concepts & Practice
